Delineation of the protective action of zinc sulfate on ulcerative colitis in rats

Ho H. Luk, Joshua KO, Hon S. Fung, Chi H. Cho*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)

Abstract

The protective action of zinc compounds in Crohn's disease-like inflammatory bowel disease in animals has been shown. A similar action of zinc sulfate on ulcerative colitis has not been defined. The present study aimed to delineate the protective action of zinc sulfate and the pathogenic mechanisms of 2,4-dinitrobenzene sulfonic acid (DNBS)-induced ulcerative colitis in rats. Zinc sulfate at different concentrations was given either orally (p.o.) or rectally (p.r.) to rats at 42, 48, 66 and 72 h following the induction of colonic inflammation by DNBS. Rats were killed 96 h after instillation of DNBS rectally to assess the severity of colonic damage, myeloperoxidase and xanthine oxidase activities. The involvement of mast cell degranulation and histamine release in the pathogenesis of DNBS-induced colitis was determined by using a mast cell stabilizer (ketotifen) and histamine receptor blockers (terfenadine and ranitidine). DNBS given rectally produced inflammation and ulceration in rats with a pathology resembling ulcerative colitis. Myeloperoxidase activity but not xanthine oxidase activity was sharply increased by this agent. Intrarectal administration of zinc solution and parenteral injection of histamine blockers significantly reduced tissue damage and myeloperoxidase but not xanthine oxidase activity. Ketotifen, a mast cell stabilizer, also significantly decreased mucosal injury and myeloperoxidase activity in the colon. In conclusion, mast cell degranulation followed by histamine release plays an important role in the pathogenesis of DNBS-induced ulcerative colitis. Zinc given rectally has a therapeutic effect against this colitis model, perhaps through the reduction of inflammation and inhibition of the above pathogenic mechanisms.

Original languageEnglish
Pages (from-to)197-204
Number of pages8
JournalEuropean Journal of Pharmacology
Volume443
Issue number1-3
DOIs
Publication statusPublished - 17 May 2002

Scopus Subject Areas

  • Pharmacology

User-Defined Keywords

  • 2,4-dinitrobenzene sulfonic acid (DNBS)
  • Histamine
  • Ketotifen
  • Mast cell
  • Neutrophil
  • Ranitidine
  • Reactive oxygen metabolite
  • Terfenadine
  • Ulcerative colitis
  • Zinc sulfate

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